title: Ghrelin inhibits AGEs-induced apoptosis in human endothelial cells involving ERK1/2 and PI3K/Akt pathways.
abstract: Endothelial dysfunction caused by cell apoptosis is thought to be a major cause of diabetic vascular complications. Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic vascular complications by inducing apoptosis of endothelial cells. The aim of this study was to explore the effect of ghrelin on AGEs-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs) and the potential mechanisms involved in this process. Exposure to AGEs (200 mg l(-1) ) for 48 h caused a significant increase in cell apoptosis, while pretreatment with ghrelin eliminated AGEs-induced apoptosis in HUVECs, as evaluated by MTT assays, flow cytometry and Hoechst 33258 staining. The induction of caspase-3 activation was also prevented by ghrelin in cells incubated with AGEs. Exposure to ghrelin (10(-6)  M) resulted in a rapid activation of extracellular signal-regulated protein kinase (ERK)1/2 and Akt. The inhibitory effect of ghrelin on caspase-3 activity was attenuated by inhibitors of ERK1/2 (PD98059), PI3K/Akt (LY294002) and growth hormone secretagogue receptor (GHSR)-1a (D-Lys(3) -growth hormone releasing peptide-6). The results of this study indicated that ghrelin could inhibit AGEs-mediated cell apoptosis via the ERK1/2 and PI3K/Akt pathways and GHSR-1a was also involved in the protective action of ghrelin in HUVECs. As such, ghrelin demonstrates significant potential for preventing diabetic cardiovascular complications.
authors.affiliation: Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Menglan
authors.initials: M
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Can
authors.initials: C
authors.lastname: Cui
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D054439:Ghrelin / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D054439:Ghrelin; D017127:Glycation End Products, Advanced; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3